Mark A. Warner, M.D. (Chair) Rochester, Minnesota. Robert A. Caplan, M.D. Seattle, Washington. Burton S. Epstein, M.D.

Transcription

1 Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures A Report by the American Society of Anesthesiologists Developed by the Task Force on Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration Mark A. Warner, M.D. (Chair) Rochester, Minnesota Robert A. Caplan, M.D. Seattle, Washington Burton S. Epstein, M.D. Washington, DC Charles P. Gibbs, M.D. Denver, Colorado Candace E. Keller, M.D., M.P.H. Hattiesburg, Mississippi Jessie A. Leak, M.D. Fayetteville, North Carolina Roger Maltby, M.B.B.S. Calgary, Alberta David G. Nickinovich, Ph.D. Bellevue, Washington Mark S. Schreiner, M.D. Philadelphia, Pennsylvania Chris M. Weinlander, M.D. Appleton, Wisconsin

2 Introduction Practice guidelines are systematically developed recommendations that assist the practitioner and patient in making decisions about health care. These recommendations may be adopted, modified, or rejected according to clinical needs and constraints. Practice guidelines are not intended as standards or absolute requirements. The use of practice guidelines cannot guarantee any specific outcome. Practice guidelines are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. The guidelines provide basic recommendations that are supported by analysis of the current literature and by a synthesis of expert opinion, open forum commentary, and clinical feasibility data (Appendix). Purposes of the Guidelines The purposes of these Guidelines are to enhance the quality and efficiency of anesthesia care, stimulate evaluation of individual practices, and reduce the severity of complications related to pulmonary aspiration of gastric contents, should it occur. Enhancements in the quality and efficiency of anesthesia care include, but are not limited to, the cost-effective utilization of perioperative preventive medication, increased patient satisfaction, avoidance of delays and cancellations, decreased risk of dehydration or hypoglycemia from prolonged fasting, and the minimization of perioperative morbidity. Complications of aspiration include, but are not limited to, aspiration pneumonia, respiratory disabilities, and related morbidities. Focus of the Guidelines Prevention of pulmonary aspiration is part of the larger process of preoperative evaluation and preparation of the patient. The Guidelines specifically focus on preoperative fasting recommendations, as well as recommendations regarding the administration of pharmacologic agents to modify the volume and acidity of gastric contents during procedures in which upper airway protective reflexes may be impaired. Airway management techniques that are intended to reduce the occurrence of pulmonary aspiration are not the focus of these Guidelines. For example, a rapid-sequence induction/endotracheal intubation technique or awake endotracheal intubation technique may be useful to prevent this problem during the delivery of anesthesia care. The Guidelines do not address the selection of anesthetic technique. The intended patient population is limited to healthy patients of all ages undergoing elective procedures. The Guidelines do not apply to patients who undergo procedures with no anesthesia or only local anesthesia when upper airway protective reflexes are not impaired, and no risk factors for pulmonary aspiration are apparent. The Guidelines are not intended for women in labor.

3 The Guidelines may not apply to or may need to be modified for patients with co-existing diseases or conditions that might affect gastric emptying or fluid volume (e.g., pregnancy, obesity, diabetes, hiatal hernia, gastroesophageal reflux disease, ileus or bowel obstruction, emergency care, or enteral tube feeding) and patients in whom airway management might be difficult. Anesthesiologists and other anesthesia providers should recognize these conditions and minimize the opportunity for regurgitation and pulmonary aspiration. Application of the Guidelines The Guidelines are intended for use by anesthesiologists and other anesthesia providers. They also may serve as a resource for other health care professionals who advise or care for patients who will receive anesthesia care during procedures. Anesthesia care during procedures is defined as general anesthesia, regional anesthesia, or sedation/analgesia (i.e., monitored anesthesia care). Throughout these Guidelines, the term preoperative should be considered synonymous with preprocedural, as the latter term relates to procedures commonly not considered to be operations. Task Force Members and Consultants The ASA appointed a Task Force of 10 members to (a) review the published evidence; (b) obtain consultant opinion from a representative body of anesthesiologists, nurse anesthetists, anesthesiology assistants, perioperative nurses, surgeons, gastroenterologists and other internists, dentists and oral surgeons, ophthalmologists, psychiatrists, emergency medicine physicians, and practice management staff personnel; and (c) build consensus within the Task Force. The Task Force members consisted of anesthesiologists in both private and academic practices from various geographic areas of the United States and Canada and methodologists of the ASA Practice Guidelines Project. The Task Force met its objective in a five-step process. First, original published research studies relevant to these issues were reviewed and analyzed. Second, Consultants from around the world who practice or work in various settings (e.g., academic and private practice) were asked to (a) participate in a survey of their impressions of the effectiveness of various fasting and pharmacologic interventions to decrease the risks of perioperative pulmonary aspiration, and (b) review and comment on the initial draft report of the Task Force. Third, the Task Force held an open forum at a major national anesthesia meeting to solicit input on its draft recommendations from attendees of the meeting. Fourth, all available information was used to build consensus within the Task Force on the recommended guidelines that follow. Finally, the Consultants were surveyed to assess their opinions on the feasibility of implementing the Guidelines. Availability and Strength of Evidence Evidence-based guidelines are developed by a rigorous analytic process. To assist the reader, the Guidelines make use of several descriptive terms that are easier to understand than the technical terms and data that are used in the actual analyses. These descriptive terms are defined below:

4 The following terms describe the availability of scientific evidence in the literature. Insufficient: There are too few published studies to investigate a relationship between a clinical intervention and clinical outcome. Inconclusive: Published studies are available, but they cannot be used to assess the relationship between a clinical intervention and a clinical outcome because the studies either do not meet predefined criteria for content as defined in the Focus of the Guidelines, or do not meet research design or analytic standards. Silent: There are no available studies in the literature that address a relationship of interest. The following terms describe the strength of scientific data. Supportive: Suggestive: Equivocal: There is sufficient quantitative information from adequately designed studies to describe a statistically significant relationship (P<0.01) between a clinical intervention and a clinical outcome, using the technique of meta-analysis. There is enough information from case reports and descriptive studies to provide a directional assessment of the relationship between a clinical intervention and a clinical outcome. This type of qualitative information does not permit a statistical assessment of significance. Qualitative data have not provided a clear direction for clinical outcomes related to a clinical intervention and (1) there is insufficient quantitative information or (2) aggregated comparative studies have found no quantitatively significant differences among groups or conditions. The following terms describe survey responses from Consultants for any specified issue. Responses are weighted as agree = +1, undecided = 0 or disagree = -1. Agree: The average weighted responses must equal to or greater than (on a scale of 1 to 1) to indicate agreement. Equivocal: The average weighted responses must be between and (on a scale of 1 to 1) to indicate an equivocal response. Disagree: The average weighted responses must be equal to or less than (on a scale of 1 to 1) to indicate disagreement. Guidelines I. Preoperative assessment There is insufficient published evidence to evaluate the effect of a preoperative assessment (e.g., history, physical examination, survey/interview) on the frequency or severity of pulmonary aspiration of gastric contents during the perioperative period. The Consultants and the Task Force agree that a preoperative assessment may be associated with improved outcome related to the prevention of perioperative pulmonary aspiration of gastric contents.

5 A review of pertinent medical records, a physical examination, and patient survey or interview should be performed as part of the preoperative evaluation. The history, examination, and interview should include pertinent assessment of gastroesophageal reflux disease, dysphagia symptoms, or other gastrointestinal motility disorders, potential for difficult airway management, and metabolic disorders (e.g., diabetes mellitus) that may increase the risk of regurgitation and pulmonary aspiration. Patients should be informed of fasting requirements and the reasons for them sufficiently in advance of their procedures. Verification of their compliance with the fasting requirements should be assessed at the time of their procedures. When the following fasting guidelines are not followed, the practitioner should compare the risks and benefits of proceeding, with consideration given to the amount and type of liquids or solids ingested. II. Preoperative fasting status (clear liquids) Published evidence is silent on the relationship between fasting times, gastric volume, or gastric acidity and the risk of emesis/reflux or pulmonary aspiration in humans. Studies comparing fasting times of between 2 and 4 hours versus more than 4 hours found smaller gastric volumes in adult patients who fasted 2 to 4 hours, although the effect size was small. No differences in gastric volume were found for children who fasted 2 to 4 hours versus more than four hours. In studies that examine the ingestion of clear liquids between 2 and 4 hours before procedures and in which ingested liquid volumes were recorded, participants received volumes of clear liquids ranging widely from 2 ml/kg to unrestricted amounts. Published evidence is equivocal regarding the effect of clear liquid ingestion on gastric acidity for both adults and children. The Consultants are equivocal regarding a fasting period for clear liquids of between 2 and 4 hours for adults, but they support a fasting period of 2 hours for infants and children. The Task Force supports a fasting period for clear liquids of 2 hours for all patients. It is appropriate to fast from intake of clear liquids for 2 or more hours before procedures requiring general anesthesia, regional anesthesia, or sedation/analgesia (monitored anesthesia care) [Table 1]. Examples of clear liquids include, but are not limited to, water, fruit juices without pulp, carbonated beverages, clear tea, and black coffee. These liquids should not include alcohol. The volume of liquid ingested is less important than the type of liquid ingested. III. Preoperative fasting status (breast milk) There is insufficient published evidence to evaluate the relationship of the timing of breast milk intake before procedures to the incidence of emesis/reflux or pulmonary aspiration. The Consultants and Task Force support a fasting period for breast milk of 4 hours for both neonates and infants. It is appropriate to fast from intake of breast milk for 4 or more hours before procedures requiring general anesthesia, regional anesthesia, or sedation/analgesia (i.e., monitored anesthesia care) [Table 1]

6 IV. Preoperative fasting status (infant formulae) There is insufficient published evidence to address the safety of any preoperative fasting period for infant formulae. For infants and children, the Consultants and Task Force support a fasting period of 6 hours. For neonates, the Consultants support a fasting period of 4 hours, and the Task Force supports a fasting period of 6 hours. It is appropriate to fast from intake of infant formula for 6 or more hours before elective procedures requiring general anesthesia, regional anesthesia, or sedation/analgesia (e.g., monitored anesthesia care) [Table 1]. V. Preoperative fasting status (solids and non-human milk) There is insufficient published evidence to address the safety of any preoperative fasting period for solids or non-human milk. For patients of all ages, the Consultants and Task Force support a fasting period for a light meal (e.g., toast and a clear liquid) of 6 hours before elective procedures requiring general anesthesia, regional anesthesia, or sedation/analgesia (i.e., monitored anesthesia care). They also support of a fasting period for a meal that includes fried or fatty foods or meat of 8 or more hours before elective procedures. For infants and children, the Consultants and Task Force support a fasting period of 6 hours for non-human milk. It is appropriate to fast from intake of a light meal or non-human milk for 6 or more hours before elective procedures requiring general anesthesia, regional anesthesia, or sedation/analgesia (e.g., monitored anesthesia care) [Table 1]. The Task Force notes that intake of fried or fatty foods or meat may prolong gastric emptying time. Both the amount and type of foods ingested must be considered when determining an appropriate fasting period. Since non-human milk is similar to solids in gastric emptying time, the amount ingested must be considered when determining an appropriate fasting period. VI. Preoperative gastrointestinal stimulants Published evidence supports the efficacy of gastrointestinal stimulants (e.g., metoclopramide) for reducing gastric volume during the perioperative period. It is equivocal regarding the relationship between gastrointestinal stimulants and gastric acidity. There is insufficient published evidence to examine the relationship between gastrointestinal stimulants and the frequency of pulmonary aspiration. The Consultants and Task Force are equivocal regarding the preoperative use of gastrointestinal stimulants to reduce the risks of pulmonary aspiration.

7 The routine preoperative use of gastrointestinal stimulants to decrease the risks of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended (Table 2). VII. Preoperative pharmacologic blockade of gastric acid secretion Published evidence supports the efficacy of histamine-2 receptor antagonist agents (e.g., cimetidine, famotidine, or ranitidine) to reduce gastric acidity and volume during the perioperative period and also suggests that proton pump inhibitors (e.g., omeprazole or lansoprazole) are effective for these same purposes. However, it does not sufficiently examine the relationship between reduced gastric acid secretion and the frequency of pulmonary aspiration in humans, and it is silent on the relationship between agents that block gastric acid secretion and the frequency of pulmonary aspiration. There is not sufficient published evidence to evaluate whether reduced gastric acid secretion is associated with decreased morbidity or mortality in patients who have aspirated gastric contents. The Consultants and Task Force are equivocal regarding the use of agents that block preoperative gastric acid secretion to reduce the risks of pulmonary aspiration. The routine preoperative use of medications that block gastric acid secretion to decrease the risks of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended. VIII. Preoperative antacids Published evidence supports the efficacy of preoperative antacids (e.g., sodium citrate, sodium bicarbonate, or magnesium trisilicate) for decreasing gastric acidity during the perioperative period, but it does not support their efficacy in reducing gastric volume. It does not sufficiently examine the relationship between reduced gastric acidity and the frequency of pulmonary aspiration in humans. It also does not examine the relationship between preoperative use of antacids and the frequency of emesis. There is insufficient published evidence to evaluate whether reduced gastric acidity or volume is associated with decreased morbidity or mortality in patients who have aspirated gastric contents. The Task Force agrees that the pulmonary aspiration of antacids that contain particulates, compared with those that do not, may increase the risk of pulmonary damage. The Consultants and Task Force are equivocal regarding the preoperative use of antacids. The routine preoperative use of antacids to decrease the risks of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended. Only nonparticulate antacids should be used when antacids are indicated for selected patients for purposes other than reducing the risk of pulmonary aspiration. I

8 X. Preoperative antiemetics Published evidence suggests that preoperative antiemetics (e.g., droperidol, ondansetron) reduce nausea and vomiting during the perioperative period, but statistical significance was not achieved. The literature does not sufficiently examine the relationship between nausea or vomiting and the frequency of pulmonary aspiration in humans during the perioperative period, nor does it sufficiently examine the relationship between preoperative antiemetics and the frequency of pulmonary aspiration. The Consultants and Task Force are equivocal regarding the preoperative use of antiemetics. These Guidelines do not address the use of antiemetics during the extended postoperative period after upper airway protective reflexes are no longer impaired. The routine preoperative use of antiemetics to reduce the risks of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended. X. Preoperative anticholinergics Published evidence is equivocal regarding the use of anticholinergics (e.g., atropine, scopolamine, or glycopyrrolate) to decrease gastric volume or acidity. The Consultants and Task Force agree that the preoperative use of anticholinergics is not associated with improved outcomes related to pulmonary aspiration. The use of anticholinergics to decrease the risks of pulmonary aspiration is not recommended. XI. Preoperative multiple agents Published evidence supports the preoperative effectiveness of multiple agents, such as histamine-2 receptor antagonists, gastrointestinal stimulants, and antacids, to decrease gastric volume and acidity. However, it is equivocal regarding the added benefit of multiple agents when compared with single agents. It also does not sufficiently examine the relationship between reduced gastric volume or acidity and the frequency of pulmonary aspiration in humans, and it is silent on the relationship between combined pharmacologic agents and the frequency of pulmonary aspiration. There is not sufficient published evidence to evaluate whether reduced gastric volume or acidity is associated with decreased morbidity or mortality in patients who have aspirated gastric contents. The Consultants and Task Force are equivocal regarding the use of multiple pharmacologic agents to reduce the frequency or severity of complications associated with pulmonary aspiration. Recommendations The routine preoperative use of multiple agents in patients who have no apparent increased risk for pulmonary aspiration is not recommended.

9 Table 1. Summary of Fasting Recommendations to Reduce the Risk of Pulmonary Aspiration 1 Ingested Material Minimum Fasting Period 2 Clear liquids 3 Breast milk Infant formula 2 h 4 h 6 h Non-human milk 4 Light meal 5 6h 6h 1 These recommendations apply to healthy patients who are undergoing elective procedures. They are not intended for women in labor. Following the guidelines does not guarantee a complete gastric emptying has occurred. 2 The fasting periods noted above apply to all ages. 3 Examples of clear liquids include water, fruit juices without pulp, carbonated beverages, clear tea, and black coffee. 4 Since non-human milk is similar to solids in gastric emptying time, the amount ingested must be considered when determining an appropriate fasting period. 5 A light meal typically consists of toast and clear liquids. Meals that include fried or fatty foods or meat may prolong gastric emptying time. Both the amount and type of foods ingested must be considered when determining an appropriate fasting period.

10 Table 2. Summary of Pharmacologic Recommendations to Reduce the Risk of Pulmonary Aspiration Medication Type and Common Examples Recommendation Gastrointestinal stimulants metoclopramide No routine use Gastric acid secretion blockers cimetidine famotidine ranitidine omeprazole lansoprazole No routine use Antacids sodium citrate sodium bicarbonate magnesium trisilicate No routine use Antiemetics droperidol ondansetron No routine use Anticholinergics atropine scopolamine glycopyrrolate No use Combinations of the medications above No routine use

11 Appendix: Methods and Analyses The scientific assessment of these Guidelines was based on the following statements, or evidence linkages. These linkages represent directional statements about relationships between preoperative fasting and pharmacologic prophylaxis of pulmonary aspiration and clinical outcomes. 1. A preoperative assessment (e.g., history, physical exam, survey/interview): a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 2. For adults, preoperative fasting status of solids between 4 and 8 hours: a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 3. For adults, preoperative fasting status of liquids between 2 and 4 hours: a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 4. For children, infants and neonates, preoperative fasting status of milk, breast milk or formula between 2 and 4 hours: a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 5. Preoperative gastrointestinal stimulants: a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 6. Preoperative pharmacologic blockage of gastric acid secretion (i.e., histamine-2 receptor antagonists and proton pump inhibitors): a) increases patient comfort, b) reduces adverse outcomes, c) improves patient satisfaction, and d) improves cost/utilization of services. 7. Preoperative antacids: a) increase patient comfort, b) reduce adverse outcomes, c) improve patient satisfaction, and d) improve cost/utilization of services. 8. Preoperative antiemetics: a) increase patient comfort, b) reduce adverse outcomes, c) improve patient satisfaction, and d) improve cost/utilization of services. 9. Preoperative anticholinergics: a) increase patient comfort, b) reduce adverse outcomes, c) improve patient satisfaction, and d) improve cost/utilization of services. 10. Preoperative multiple agents (e.g., triple prophylaxis): a) increase patient comfort, b) reduce adverse outcomes, c) improve patient satisfaction, and d) improve cost/utilization of services. Scientific evidence was derived from aggregated human research literature, with meta-analyses utilized when appropriate, and from surveys, open presentations and other consensus-oriented activities. For purposes of literature aggregation, potentially relevant clinical studies were identified via electronic and manual searches of the literature. The electronic search covered a 31-year period from 1966 through The manual search covered a 57-year period of time from 1940 through Over 3000 citations were initially identified, yielding a total of 1156 non-overlapping articles that addressed topics related to the 10 evidence linkages. Following review of the articles, 924 studies did not provide direct evidence, and were subsequently eliminated. A total of 232 articles (from 48 journals) contained direct linkage-related evidence. The literature was first categorized according to the proximity or directness of the outcome to the intervention. Generally, a study should either evaluate a direct comparison or institute methodologic controls (e.g., control for intervening variables) in order to appropriately evaluate an outcome. For these Guidelines, the primary outcome of interest was either pulmonary aspiration or the adverse consequences from aspiration. Therefore, comparison of an intervention with pulmonary aspiration or comparison of an intervention with an adverse consequence from aspiration (e.g., pneumonitis) was the focus of these Guidelines. However, the lit-

12 erature was generally not sufficient to evaluate such relationships. The literature revealed four types of analytic relationships between interventions and outcomes of interest. These types of relationships are referred to as first, second, third, or fourth-order comparisons (Table 3). A first-order comparison represents a direct comparison either between an intervention (e.g., antacid administration) and a clinical outcome, or between two outcomes. In the studies reviewed with first-order comparisons, the relationship between one of the identified interventions in the Guidelines and pulmonary aspiration were not assessed. Therefore, cause-and-effect relationships between an intervention of interest and pulmonary aspiration cannot be shown. Although these outcomes (e.g., gastric volume or ph) were often considered by the authors to be representative of a predicted risk of pulmonary aspiration, results of such comparisons were not sufficient to provide methodologically acceptable evidence. Levels 2 through 4 represent comparisons that must first control for an intermediate outcome. For example, in order to examine the effectiveness of a histamine-2 receptor antagonist on pulmonary aspiration, the effect of the histamine-2 receptor antagonist on gastric content as well as the occurrence of emesis must be methodologically controlled. The gastric content and emesis outcomes are intervening steps between the intervention and pulmonary aspiration. This example would be considered a third-order comparison. Level 2 represents a comparison in which one step, or intermediate outcome exists between the intervention and the outcome of interest. However, level 2 relationships do not examine the association between an intervention of interest and the occurrence of pulmonary aspiration.

13 Table 3: Summary of First, Second, Third and Fourth-Order Comparisons of Outcomes related to Fasting and Pharmaceutical Interventions Fasting or Pharmaceutical Number of Intervention Studies First-order comparisons: 1a. Intervention - Gastric Outcomes 194 1b. Gastric Volume or ph - Emesis/Reflux 2 1c. Emesis/Reflux Pulmonary Aspiration 0 1d. Pulmonary Aspiration - Adverse Outcomes 5 Second-order comparisons: 2a. Intervention - Emesis/Reflux 7 2b. Gastric Volume or ph Pulmonary Aspiration 2 2c. Emesis/Reflux - Adverse Outcomes 0 Third-order comparisons: 3a. Intervention Pulmonary Aspiration 4 3b. Gastric volume or ph - Adverse Outcomes 0 Fourth-order comparisons: 4. Intervention - Adverse Outcomes 0 Level 3 contains one relationship of interest to the Guidelines (i.e., intervention/ pulmonary aspiration), and Level 4 contains the other relationship of interest to the Guidelines (i.e., the association between an intervention and clinical consequences from pulmonary aspiration). Table 3 indicates that outcomes related to preoperative fasting and the administration of pharmacologic agents were insufficient to evaluate cause-and-effect relationships that link the interventions of interest in these Guidelines with the occurrence of pulmonary aspiration or the clinical consequences from pulmonary aspiration. Although the literature was not sufficient for causal assessment related to pulmonary aspiration, the efficacy of the interventions of interest regarding intermediate outcomes are reported below. For these purposes, a directional result for each study was initially determined by classifying the outcome as either supporting a linkage, refuting a linkage, or neutral. The results were then summarized to obtain a directional assessment of

14 support for each linkage. The literature relating to eight evidence linkages contained enough studies with well-defined experimental designs and statistical information to conduct formal meta-analyses. These eight linkages were: linkage 3a [preoperative fasting status of liquids between 2 and 4 hours for adults], 3b [preoperative fasting status of liquids between 2 and 4 hours for children], 5 [preoperative gastrointestinal stimulants], 6 [preoperative histamine-2 receptor antagonists], 7 [preoperative antacids], 8 [preoperative antiemetics], 9 [preoperative anticholinergics], and 10 [preoperative multiple agents versus single agents]. Outcomes for all of the above linkages consisted of gastric volume, ph, gastric secretions, or nausea and vomiting. Combined probability tests were applied to continuous data, and an odds-ratio procedure was applied to dichotomous study results. Two combined probability tests were employed as follows: (1) The Fisher Combined Test, producing chi-square values based on logarithmic transformations of the reported p-values from the independent studies, and (2) the Stouffer Combined Test, providing weighted representation of the studies by weighting each of the standard normal deviates by the size of the sample. A procedure based on the Mantel-Haenszel method for combining study results using 2 X 2 tables was available for use with outcome frequency information. An acceptable significance level was set at p < 0.01 (one-tailed) and effect size estimates were calculated. Interobserver agreement was established through assessment of interrater reliability testing. Tests for heterogeneity of the independent samples were conducted to assure consistency among the study results. To control for potential publishing bias, a fail-safe N value was calculated for each combined probability test. No search for unpublished studies was conducted, and no reliability tests for locating research results were done. Results of the combined probability tests are reported in Table 4. Significance levels from the Fisher and weighted Stouffer Combined Tests for gastric volume were significant for linkages 3a (preoperative fasting status of liquids between 2 and 4 hours for adults), and 6 (preoperative histamine-2 receptor antagonists). Significance levels for gastric ph were significant for linkages 6 (preoperative histamine-2 receptor antagonists) and 7 (preoperative antacids). Significance levels for gastric volume and airway/salivary secretions were significant for linkage 9 (preoperative anticholinergics). Weighted effect size estimates for these linkages ranged from r = 0.17 to r = 0.40, demonstrating moderate effect size estimates. Tests for heterogeneity of statistical tests and effect size were non-significant for: a) gastric volume outcomes; linkages 3a, 3b, 5, 7, and 10; b) gastric ph outcomes; linkages 3a, 3b, 5, 6, 7, 9, and 10; for gastric volume and airway/salivary secretions; linkage 9; for nausea and vomiting; linkage 8. These findings indicate that the pooled studies provided common estimates of significance and population effect sizes. Tests for heterogeneity of statistical tests and for effect size were significant for linkage 6 (gastric volume). These findings may reflect the differential influence of the various types of histamine-2 receptor antagonists (e.g., cimetidine, ranitidine, famotidine), and further analysis may need to separate the distinct influence on gastric volume of each agent. Agreement among Task Force members and two methodologists was established by interrater reliability testing. Agreement levels using a Kappa statistic for two-rater agreement pairs were as follows: (1) type of study design, k = 0.75 to 0.95; (2) type of analysis, k = 0.54 to 0.85; (3) evidence linkage assignment, k = 0.68 to 0.82; and (4) literature inclusion for database, k = 0.64 to Three-rater chance-corrected agreement values were: (1) design, Sav = 0.81, Var (Sav) = 0.006; (2) analysis, Sav = 0.66, Var (Sav) = 0.014; (3) linkage identification, Sav = 0.75, Var (Sav) = 0.005; (4) literature database inclusion, Sav = 0.67, Var (Sav) =

15 These values represent moderate to high levels of agreement. The findings of the literature analyses were supplemented by the opinions of Task Force members as well as by surveys of the opinions of a panel of Consultants as described in the text of the Guidelines (N = 92). The rate of return was 84% (N = 77/92). The percentage of Consultants supporting each linkage is reported in Table 5. Consultants, in general, were highly supportive (i.e., they agreed that the specified linkage reduced the risk of adverse outcomes) of linkage 1 (preoperative assessment) and linkage 3b (2-4 hour fasting of clear liquids for children). Consultants believed that each of the 10 linkages were important issues for the Guidelines to address). Consultants generally did not agree with linkage 2 (4-8 hour fasting of solids for adults), linkage 4 (2-4 hour fasting of milk for infants), and linkage 9 (preoperative anticholinergics). A second survey addressing fasting periods for liquids, breast milk, infant formula, non-human milk and solids was conducted. The rate of return was 76% (N = 84/110). The percentage of Consultants indicating a specific number of fasting hours is reported in Table 6. For clear liquids, the Consultants indicated support for a 2-hour fasting period for both infants and children. For breast milk, the Consultants indicated support for a 4-hour fasting period for both neonates and infants. For infant formula, the Consultants indicated support for a 4-hour fasting period for neonates, and a 6-hour fasting period for infants. For non-human milk, a 6-hour fasting period was supported for both infants and children. For solids, a 6-hour fasting period was supported for infants and children. For a light meal, the Consultants indicated support for a 6-hour fasting period for adults. For a meal of meat, milk, or fried foods, an 8-hour fasting period was supported for adults. The Consultants were asked to indicate which, if any, of the evidence linkages would change their clinical practices if the Guidelines were instituted. The percent of Consultants expecting no change associated with each linkage were as follows: preoperative assessment - 95%; preoperative fasting of solids - 75%; preoperative fasting of liquids - 67%; preoperative fasting of breast milk - 78%; gastrointestinal stimulants - 95%; pharmacologic blockage of gastric secretion - 91%; antacids - 100%; antiemetics - 98%, anticholinergics - 100%, and multiple agents - 98%. Ninety-six percent of the respondents indicated that the Guidelines would have no effect on the amount of time spent on a typical case. For all respondents, the mean increase in the amount of time spent on a typical case was 2.4 minutes. Two respondents reported that the Guidelines would increase the amount of time spent per case. The anticipated increase for these two respondents, respectively, was 5 minutes and 120 minutes. * Readers with special interest in the statistical analyses used in establishing these Guidelines can receive further information by writing to the American Society of Anesthesiologists: 520 North Northwest Highway, Park Ridge, Illinois

16 Table 4: Statistical Summary: Combined Test Results Gastric Volume Linkage #3a: Preoperative Fasting Status of Liquids between 2 and 4 Hours for Adults Fisher Combined Test: χ 2 = p <.001 df = 18 Stouffer Combined Test: Effect Size Estimate: Z c (weighted) r (weighted) = = p <.010 Fail-Safe N Value: Nfs 0.01 = 22 Linkage #3b: Preoperative Fasting Status of Liquids between 2 and 4 Hours for Children Fisher Combined Test: χ 2 = p >.100 (NS) df = 18 Stouffer Combined Test: Zc (weighted) = p >.100 (NS) Effect Size Estimate: r (weighted) = 0.13 Linkage #5: Preoperative Gastrointestinal Stimulants: Fisher Combined Test: χ 2 = p <.001 df = 20 Stouffer Combined Test: Zc (weighted) = p >.010 (NS) Effect Size Estimate: r (weighted) = 0.30 Linkage #6: Preoperative Histamine-2 Receptor Antagonists Fisher Combined Test: χ 2 = p <.001 df = 96 Stouffer Combined Test: Zc (weighted) = p <.001 Effect Size Estimate: r (weighted) = 0.24 Fail-Safe N Value: Nfs 0.01 = 856 Linkage #7: Preoperative Antacids Fisher Combined Test: χ 2 = p >.100 (NS) df =14 Stouffer Combined Test: Zc (weighted) = p >.100 (NS) Effect Size Estimate: r (weighted) = 0.05 Linkage #10: Preoperative Multiple Agents Fisher Combined Test: χ 2 = p >.100 (NS) df = 24 Stouffer Combined Test: Zc (weighted) = p <.010 Effect Size Estimate: r (weighted) = 0.07 Gastric Volume, Airway/Salivary Secretions Linkage #9: Preoperative Anticholinergics Fisher Combined Test: χ 2 = p <.001 df = 18 Stouffer Combined Test: Zc (weighted) = p <.001 Effect Size Estimate: r (weighted) = 0.17 Fail-Safe N Value: Nfs 0.01 = 22

17 Gastric ph Linkage #3a: Preoperative Fasting Status of Liquids between 2 and 4 Hours for Adults Fisher Combined Test: χ 2 = p >.100 (NS) df = 18 Stouffer Combined Test: Zc (weighted) = p >.050 (NS) Effect Size Estimate: r (weighted) = 0.04 Linkage #3b: Preoperative Fasting Status of Liquids between 2 and 4 Hours for Children Fisher Combined Test: χ 2 = p >.100 (NS) df = 22 Stouffer Combined Test: Zc (weighted) = p >.100 (NS) Effect Size Estimate: r (weighted) = 0.03 Linkage #5: Preoperative Gastrointestinal Stimulants: Fisher Combined Test: χ 2 = p >.025 (NS) df = 14 Stouffer Combined Test: Zc (weighted) = p >.100 (NS) Effect Size Estimate: r (weighted) = 0.12 Linkage #6: Preoperative Histamine-2 Receptor Antagonists Fisher Combined Test: χ 2 = p <.001 df = 110 Stouffer Combined Test: Zc (weighted) = p <.001 Effect Size Estimate: r (weighted) = 0.39 Fail-Safe N Value: Nfs 0.01 = 3915 Linkage #7: Preoperative Antacids Fisher Combined Test: χ 2 = p <.001 df =22 Stouffer Combined Test: Zc (weighted) = p <.001 Effect Size Estimate: r (weighted) = 0.22 Fail-Safe N Value: Nfs 0.01 = 55 Linkage #9: Preoperative Anticholinergics Fisher Combined Test: χ 2 = p >.100 (NS) df = 10 Stouffer Combined Test: Zc (weighted) = p >.010 (NS) Effect Size Estimate: r (weighted) = 0.09 Linkage #10: Preoperative Multiple Agents Fisher Combined Test: χ 2 = p >.100 (NS) df = 28 Stouffer Combined Test: Zc (weighted) = p <.010 Effect Size Estimate: r (weighted) = 0.05 Nausea and Vomiting Linkage #8: Preoperative Antiemetics Fisher Combined Test: χ 2 = p <.001 df = 28 Stouffer Combined Test: Zc (weighted) = p >.010 (NS) Effect Size Estimate: r (weighted) = 0.14

18 Table 5: Consultant Survey of Evidence Linkages: Weighted Responses (N = 77) Reduces Increases Improves Improves Linkages Adverse Patient Patient Cost/ Outcomes Comfort Satisfaction Utilization 1. A preoperative assessment to 8 hour fasting of solids for adults a. 2 to 4 hour fasting of liquids for adults b. 2 to 4 hour fasting of clear liquids for children to 4 hour fasting of milk for infants Preoperative gastrointestinal stimulants Preoperative gastric acid secretion blockage Preoperative antacids Preoperative antiemetics Preoperative anticholinergics Preoperative multiple drugs

19 Table 6: Consultant Fasting Survey: Percentage Agreement: (N = 84) Number of Hours > 8 Clear Liquids - Infants 11% 83% 3% 3% 0% 0% 0% 0% 0% Clear Liquids - Children 12% 78% 5% 5% 0% 0% 0% 0% 0% Breast Milk - Neonates 0% 22% 20% 54% 0% 4% 0% 0% 0% Breast Milk - Infants 0% 19% 12% 56% 0% 13% 0% 0% 0% Formula - Neonates 0% 4% 9% 48% 1% 38% 0% 0% 0% Formula - Infants 0% 1% 9% 39% 1% 48% 0% 1% 0% Non-Human Milk - Infants 0% 1% 7% 36% 1% 49% 0% 6% 0% Non-Human Milk - Children 0% 0% 3% 38% 0% 50% 0% 9% 0% Solids - Infants 0% 0% 0% 8% 1% 71% 0% 19% 0% Solids - Children 0% 0% 0% 8% 0% 64% 0% 28% 0% Light Meal - Adults 1% 8% 1% 14% 1% 65% 0% 10% 0% Meat, Milk, Fried Food - Adults 0% 1% 0% 3% 1% 15% 1% 75% 4%